P53 is a tumor suppressor that plays a central role in arresting cell growth and inducing programed cell death. Mutations of p53 are the most common genetic abnormality identified in human malignancies. Despite the significance of p53 as a regulator of cellular growth/death and its apparent role in human disease, the details regarding its biological actions remain relatively obscure.
One mechanism by which p53 is believed to act is through the "transactivation," or the coordinated turning on, of genes in response to stimuli such as cellular stress. Transactivation depends upon the ability of the p53 protein to bind to specific regions of DNA (p53 responsive elements) that are within promoter sequences adjacent to target genes. This binding may lead to either an enhancement or inhibition of target gene expression. In addition, it is believed that p53 may mediate changes in cell behavior through other mechanisms that are independent of its ability to bind DNA.
The p53 protein is itself regulated both by changes in its state of phosphorylation and by intracellular localization. In addition, it has recently become clear that there are a family of proteins, structurally and functionally related to p53, that may play a role in regulating its activity. Among these proteins are at least two truncated forms of the protein that result from alternative splicing of the messenger RNA (mRNA) encoding the C-terminal end of the native protein. Identifying new isoforms of p53 and defining how they affect cellular activity may lead to new ways of regulating cell growth and, eventually, to new diagnostic and therapeutic procedures.